Prevalence of olfactory and other developmental anomalies in patients with central hypogonadotropic hypogonadism.

[kallmann syndrome]

Hypogonadotropic hypogonadism (HH ) is a heterogeneous disease caused by mutations in several genes . Based on the presence of hyposmia /anosmia it is distinguished into Kallmann syndrome (KS ) and isolated HH . The prevalence of other developmental anomalies is not well established .We studied 36 patients with HH (31 males , 5 females , mean age 41 .5 ), 9 with familial and 27 with sporadic HH (33 congenital , 3 adult-onset ), by physical examination , smell test (BSIT Sensonics ), audiometry , renal ultrasound , and magnetic resonance imaging of the olfactory structures .Based on the smell test , patients were classified as normosmic (n = 21 , 58 .3 %) and hypo /anosmic (n = 15 , 41 .6 %). Hypoplasia /agenesis of olfactory bulbs was found in 40 % of patients (10 /25 ; 75 % hypo /anosmic , 7 .6 % normosmic , p < 0 .01 , Fisher 's test ). Remarkably , olfactory structures were normal in two anosmic patients , while one normosmic patient presented a unilateral hypoplastic bulb . Fourteen of 33 patients (42 .4 %) presented neurosensorial hearing loss of various degrees (28 .5 % hypo /anosmic , 52 .6 % normosmic , p = NS ). Renal ultrasound revealed 27 .7 % of cases with renal anomalies (26 .6 % hypo /anosmic , 28 .5 % normosmic , p = NS ). At least one midline defect was found in 50 % of the patients (53 .3 % hypo /anosmic , 47 .6 % normosmic , p = NS ), including abnormal palate , dental anomalies , pectus excavatum , bimanual synkinesis , iris coloboma , and absent nasal cartilage . Anamnestically 4 /31 patients reported cryptorchidism (25 % hypo /anosmic , 5 .2 % normosmic , p = NS ).Hypo /anosmia is significantly related to anatomical anomalies of the olfactory bulbs /tracts but the prevalence of other developmental anomalies , especially midline defects and neurosensorial hearing loss , is high both in HH and KS and independent of the presence of anosmia /hyposmia . From the clinical standpoint KS and normosmic HH should be considered as the same complex , developmental disease .